This project is designed to: a. Obtain new synthetic congeners of vinblastine and vincristine, with a better therapeutic index as antileukemic agents and particularly with decreased neurotoxicity. These compounds are obtained by a new, highly effective and stereoselective synthetic reaction sequence. b. Explore tumor specific cytotoxicity, obtained by monoclonal antibody delivery of synthetic VLB congeners which are not cytotoxic but which have full VLB activity at the biochemical level of inhibition of microtubule formation and microtubule disassembly. c. Develop site activation chemotherapy based on thermal activation of atropisomeric VLB-type pro-drugs. d. Synthesized anti-multi-drug resistant agents based on observation of such activity with non-cytotoxic VLB congeners. e. Synthesized vindolinine congeners for screening as anti-AIDS agents. f. Synthesize the anti-leukemic marine indole alkaloid manzamine A and analogues for anticancer evaluation. g. Provide syntheses of compounds in the strychnine, akuammicine and tubotaiwin classes of alkaloids for anti-cancer and HIV evaluation.